crossing96/oncoscreening huggingface dataset:
Identification and Validation of Prognostic Model for Tumor Microenvironment-Associated Genes in Bladder Cancer Based on Single-Cell RNA Sequencing Data Sets.	PURPOSE: The purpose of this study was to elucidate the relationship between the tumor microenvironment (TME) and cellular diversity in bladder cancer (BLCA) progression, leveraging single-cell RNA sequencing (scRNA-seq) data to identify potential prognostic biomarkers and construct a prognostic model for BLCA. METHODS: We analyzed scRNA-seq data of normal and tumor bladder cells from the Gene Expression Omnibus (GEO) database to uncover crucial markers within the bladder TME. The study compared gene expression in normal versus tumor bladder cells, identifying differentially expressed genes. These genes were subsequently assessed for their prognostic significance using patient follow-up data from The Cancer Genome Atlas. Prognostic models were constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression analyses, focusing on eight genes of interest. The predictive performance of the model was also tested against additional GEO data sets (GSE31684, GSE13507, and GSE32894). RESULTS: The prognostic model demonstrated reliable prediction of patient outcomes. Validation through gene set enrichment analysis and immune cell infiltration assessment supported the model's efficacy. The results from both the univariate and multivariate analyses suggest that the risk score is an independent prognostic factor with a hazard ratio of 2.97 (95% CI, 2.28 to 3.9, P < .001). In the validation cohort, the AUC at 1, 2, and 3 years is 0.74, 0.74, and 0.72, respectively. CONCLUSION: Our findings proposed biomarkers with prognostic potential, laying the groundwork for future in vitro validation and therapeutic exploration. This contributes to a deeper understanding of the genes associated with bladder TME and may improve prognostic precision in BLCA management.	bladder
Long-Term Results of Bladder Preservation With Twice-Daily Radiation Plus 5-Fluorouracil/Cisplatin or Daily Radiation Plus Gemcitabine for Muscle-Invasive Bladder Cancer-Updated Report of NRG/RTOG 0712: A Randomized Phase 2 Trial.	PURPOSE: For bladder-sparing treatment of muscle-invasive bladder cancer, 5-fluorouracil/cisplatin with twice-daily radiation (FCT) or gemcitabine plus daily radiation (GD) are effective chemoradiation (CRT) regimens. This trial evaluated these regimens and demonstrated efficacy with either regimen at 3 years. With further follow-up, longer-term results are reported here. METHODS AND MATERIALS: Patients with cT2 to cT4a muscle-invasive bladder cancer were randomized to FCT or GD. Patients had a transurethral resection and induction CRT to 40 Gy. Patients with a complete response received consolidation CRT to 64 Gy. Others had cystectomy. Adjuvant gemcitabine/cisplatin chemotherapy was administered. The primary endpoint was freedom from distant metastasis (FDM). This updated analysis reports 7-year data. Toxicity and efficacy endpoints, including bladder-intact distant metastasis-free survival (BI-DMFS) were also assessed. RESULTS: From December 2008 to April 2014, 70 patients were enrolled; 66 were eligible for analysis, 33 per arm. Median follow-up was 9.1 years for eligible living patients. At 7 years, FDM was 65% and 73% for FCT and GD, respectively. Bladder-intact distant metastasis-free survival was 58% (95% CI, 41-76) and 68% (95% CI, 51-84), respectively. The post hoc hazard ratio of 0.75 (95% CI, 0.37-1.55) showed no difference between treatments (P = .44). Overall survival at 7 years was 48% and 59%. There were 4 and 5 cystectomies performed for FCT and GD, respectively. In the FCT arm, there were 5 (16%), 1 (3%), and 0 grade 3, 4, and 5 late toxicities reported, respectively. In the GD arm, there were 7 (23%), 0, and 0 grade 3, 4, and 5 late toxicities reported, respectively. CONCLUSIONS: Both regimens maintained high FDM rates at 7 years. Cystectomy rates were low and overall survival rates were high on both arms. Late toxicity rates were low. Either gemcitabine and daily radiation or a cisplatin-based regimen are effective bladder-sparing therapies.	bladder
Genomic patterns of somatic mutations provide new prognostic, therapeutic, and biological insights in cancer.	The mutational landscape of an individual's cancer can inform on its molecular state and be used as prognostic and therapeutic markers. The study by Barbour et al.(1) analyzes mutational patterns in bladder cancer samples to uncover new biological insights into the ERCC2 gene function and develop new predictive prognostic tools.	bladder
Higher genetically predicted triglyceride level increases the bladder cancer risk independent of LDL and HDL levels.	The causal relationship between lipid levels and bladder cancer is still inconclusive currently. We aimed to reveal the causal relationship between triglycerides, HDL, and LDL and the risk of bladder cancer by univariable and multivariable Mendelian randomization (MR) analysis. The single nucleotide polymorphisms (SNPs) of exposure (triglycerides: 441,016 samples; HDL: 403,943 samples; LDL: 440,546 samples) were obtained from UK Biobank. The Genetic variation related to bladder cancer included 1554 cases and 359,640 controls. Univariable and multivariable MR methods were conducted with subsequent analysis, and smoking was regarded as a confounder. The inverse-variance weighted (IVW), MR-Egger, weighted-median method, Cochran's Q test, and MR-PRESSO were considered the main MR analysis and sensitivity analysis methods. Univariable MR analysis results suggested the triglycerides level (P = 0.011, OR = 1.001, 95% CI = 1.000-1.002) was causally associated with increased risk of bladder cancer. Multivariable MR results indicated that higher triglyceride levels could still increase the risk of bladder cancer after adjusting the effects of HDL, LDL, and smoking (P = 0.042, OR = 1.001, 95% CI = 1.000-1.002). Our findings supported that triglyceride level is causally associated with an increased risk of bladder cancer independent of LDL and HDL at the genetic level. Timely attention to changes in blood lipid levels might reduce the risk of bladder cancer.	bladder
Integrated ceRNAs regulating relationship and bioinformatics analysis to study the molecular mechanisms of the inhibition of puerarin on bladder cancer cell.	Based on previous experiments, we demonstrated puerarin inhibited the proliferation of BC T24 cells. To further explore the molecular mechanisms, whole transcriptome sequencing combined with bioinformatics analysis was performed. The results showed puerarin significantly inhibited T24 proliferation and pathway enrichment analysis of differentially expressed RNAs were mainly enriched in Cell cycle, PI3K/AKT, Ras family chromatin remodeling. lncRNAs and circRNAs may regulate miRNAs, thereby regulating the expression of ITGA1, PAK2 and UTRN. The predicted upstream transcription factor ERG and puerarin were well docked, which may be one of the underlying mechanisms by which puerarin inhibiting BC cells.	bladder
Excluding confusable diseases in patients with presumptive diagnosis of interstitial cystitis: A large patient cohort study.	OBJECTIVE: To analyze the results of excluding confusable diseases in patients with a presumptive diagnosis of interstitial cystitis (IC). METHODS: We retrospectively reviewed the electronic medical records of consecutive patients with IC between October 2005 and December 2019. RESULTS: Patients with pelvic pain underwent an initial workup. Of these, 646 patients (164 men, 25.4%; 482 women, 74.6%) underwent observational cystoscopy under the suspicion of IC. Fourteen patients had genitourinary tract malignancies (2.2%) (bladder cancer, n = 13; prostate cancer, n = 1). Of the 13 patients with bladder cancer, three were diagnosed during initial observation cystoscopy. The remaining 10 patients were diagnosed during subsequent follow-up cystoscopic surgery. Urinary tuberculosis was identified in seven (1.1%) of 646 patients during the examination. Five (0.8%) of the six patients with suspected urinary tuberculosis at baseline imaging were positive for tuberculosis in the acid-fast bacillus test. One patient developed tuberculous granulomas in the bladder tissue after a cystectomy for intractable pelvic pain. CONCLUSION: Our results show that continuous efforts to rule out bladder tumors or tuberculosis are still essential in the follow up of patients with suspected IC, even if these diseases are not excluded at the initial examination. Imaging studies are necessary to rule out tuberculosis.	bladder
Impact of intra-tumoral immunity on predicting response and survival after neoadjuvant cisplatin-based chemotherapy in patients with muscle invasive bladder cancer.	BACKGROUND: Neoadjuvant cisplatin-based chemotherapy (NAC) followed by cystectomy is the standard of care for patients with muscle-invasive bladder cancer (MIBC). Pathologic complete response (pCR) is associated with favorable outcomes, but only 30%-40% of patients achieve that response. The aim of this study is to investigate the role played by the Tumor and Immune Microenvironment (TIME) in association with the clinical outcome of patients with MIBC undergoing NAC. METHODS: Nineteen patients received NAC and were classified as pCR (n = 10) or non-pCR (n = 9). Bulk RNA-seq and immune protein evaluations using Digital Spatial Profiling (DSP) were performed on formalin-fixed paraffin-embedded (FFPE) tumor biopsies collected before NAC (baseline). Immunohistochemistry (IHC) evaluation focused on CD3 and CD20 expression was performed on baseline and end-of-treatment (EOT) FFPEs. Baseline peripheral blood was assessed for lymphocyte and neutrophil counts. Kaplan-Meier analyses and Cox PH regression models were used for survival analyses (OS). RESULTS: In the periphery, pCR patients showed lower neutrophil counts, and neutrophil/ lymphocyte ratio (NLR) when compared to non-pCR patients. In the tumor microenvironment (TME), gene expression analysis and protein evaluations highlighted an abundance of B cells and CD3(+) T cells in pCR versus non-pCR patients. On the contrary, increased protein expression of ARG1(+) cells, and cells expressing immune checkpoints such as LAG3, ICOS, and STING were observed in the TME of patients with non-pCR. CONCLUSIONS: In the current study, we demonstrated that lower NLR levels and increased CD3(+) T cells and B cell infiltration are associated with improved response and long-term outcomes in patients with MIBC receiving NAC. These findings suggest that the impact of immune environment should be considered in determining the clinical outcome of MIBC patients treated with NAC.	bladder
Tranexamic acid reduces perioperative blood transfusions following open radical cystectomy - a propensity-score matched analysis.	PURPOSE: Radical cystectomy is associated with bleeding and high transfusion rates, presenting challenges in patient management. This study investigated the prophylactic use of tranexamic acid during radical cystectomy. METHODS: All consecutive patients treated with radical cystectomy at a tertiary care university center were included from a prospectively maintained database. After an institutional change in the cystectomy protocol patients received 1 g of intravenous bolus of tranexamic acid as prophylaxis. To prevent bias, propensity score matching was applied, accounting for differences in preoperative hemoglobin, neoadjuvant chemotherapy, tumor stage, and surgeon experience. Key outcomes included transfusion rates, complications, and occurrence of venous thromboembolism. RESULTS: In total, 420 patients were included in the analysis, of whom 35 received tranexamic acid. After propensity score matching, 32 patients and 32 controls were matched with regard to clinicopathologic characteristics. Tranexamic acid significantly reduced the number of patients who received transfusions compared to controls (19% [95%-Confidence interval = 8.3; 37.1] vs. 47% [29.8; 64.8]; p = 0.033). Intraoperative and postoperative transfusion rates were lower with tranexamic acid, though not statistically significant (6% [1.5; 23.2] vs. 19% [8.3; 37.1], and 16% [6.3; 33.7] vs. 38% [21.9; 56.1]; p = 0.257 and p = 0.089, respectively). The occurrence of venous thromboembolism did not differ significantly between the groups (9% [2.9; 26.7] vs. 3% [0.4; 20.9]; p = 0.606). CONCLUSION: Prophylactic tranexamic administration, using a simplified preoperative dosing regimen of 1 g as a bolus, significantly lowered the rate of blood transfusion after cystectomy. This exploratory study indicates the potential of tranexamic acid in enhancing outcomes of open radical cystectomy.	bladder
Current Status of Magnetic Resonance Imaging Use in Bladder Cancer.	Bladder cancer (BC) is a significant global health concern, with over 500,000 new cases and 200,000 deaths annually, emphasizing the need for accurate staging and effective management. Traditional diagnostic techniques, such as cystoscopy and transurethral resection, are fundamental but have limitations in accurately assessing the depth of invasion. These limitations include the possibility of understaging and procedural variability, which can significantly impact treatment decisions. This review focuses on the role of multiparametric magnetic resonance imaging (mpMRI) in the diagnosis and staging of BC, particularly emphasizing the Vesical Imaging-Reporting and Data System (VI-RADS) framework. By enhancing interpretive consistency and diagnostic accuracy, mpMRI and VI-RADS offer detailed visualization of tumor characteristics and depth of invasion, while reducing the need for more invasive traditional methods. These advancements not only improve staging accuracy but also enhance treatment planning, underscoring the importance of advanced imaging in evolving BC management and positively influencing patient outcomes.	bladder
Patient-derived bladder cancer organoids show stable transcript expression along cultivation.	INTRODUCTION: Bladder cancer (BC) is a prevalent malignancy with high recurrence rates. Patient-derived bladder cancer organoids (BCO) pose as a promising approach in both, disease modeling and individualized treatment screening. The aim of this study was to investigate the transcriptomic plasticity in BCOs as a function of cultivation times to define ideal time periods for the applications envisioned. METHODS: Tumor samples of three patients with pathologically confirmed non-muscle invasive and muscle-invasive bladder cancer were included in this study and expanded as BCOs. RNA expression was investigated at different time periods of cells in culture using differential gene expression for overall transcript expression and quantitative real-time PCR (qRT-PCR) for pathological relevant markers. RESULTS: Differential gene expression of the BCO lines was investigated across passages 1-4, in passages 5-9 and above 9, respectively. Analysis of the entire transcriptome of the respective BCO lines revealed consistent profiles without significant alterations throughout the cultivation and expansion procedure. Notably, key transcripts like TP53, PIK3CA, BRCA1, among others, exhibited stable expression levels in the quantitative RNA analysis during the cultivation period. CONCLUSION: The robust transcriptome during BCO cultivation advocates for the use of earlier passages of BCOs in personalized medicine providing a time-efficient drug screening option to accelerate the counseling of patients' treatment options. Higher passages of BCOs still hold the potential in topics demanding for expanded cell masses such as medical device development and others.	bladder
Advancing bladder cancer management: development of a prognostic model and personalized therapy.	BACKGROUND: Bladder cancer (BLCA) was recognized as a significant public health challenge due to its high incidence and mortality rates. The influence of molecular subtypes on treatment outcomes was well-acknowledged, necessitating further exploration of their characterization and application. This study was aimed at enhancing the understanding of BLCA by mapping its molecular heterogeneity and developing a robust prognostic model using single-cell and bulk RNA sequencing data. Additionally, immunological characteristics and personalized treatment strategies were investigated through the risk score. METHODS: Single-cell RNA sequencing (scRNA-seq) data from GSE135337 and bulk RNA-seq data from several sources, including GSE13507, GSE31684, GSE32894, GSE69795, and TCGA-BLCA, were utilized. Molecular subtypes, particularly the basal-squamous (Ba/Sq) subtype associated with poor prognosis, were identified. A prognostic model was constructed using LASSO and Cox regression analyses focused on genes linked with the Ba/Sq subtype. this model was validated across internal and external datasets to ensure predictive accuracy. High- and low-risk groups based on the risk score derived from TCGA-BLCA data were analyzed to examine their immune-related molecular profiles and treatment responses. RESULTS: Six molecular subtypes were identified, with the Ba/Sq subtype being consistently associated with poor prognosis. The prognostic model, based on basal-squamous subtype-related genes (BSSRGs), was shown to have strong predictive performance across diverse clinical settings with AUC values at 1, 3, and 5 years indicating robust predictability in training, testing, and entire datasets. Analysis of the different risk groups revealed distinct immune infiltration and microenvironments. Generally higher tumor mutation burden (TMB) scores and lower tumor immune dysfunction and exclusion (TIDE) scores were exhibited by the low-risk group, suggesting varied potentials for systemic drug response between the groups. Finally, significant differences in potential systemic drug response rates were also observed between risk groups. CONCLUSIONS: The study introduced and validated a new prognostic model for BLCA based on BSSRGs, which was proven effective in prognosis prediction. The potential for personalized therapy, optimized by patient stratification and immune profiling, was highlighted by our risk score, aiming to improve treatment efficacy. This approach was promised to offer significant advancements in managing BLCA, tailoring treatments based on detailed molecular and immunological insights.	bladder
Developments in conservative treatment for BCG-unresponsive non-muscle invasive bladder cancer.	INTRODUCTION: To reduce the risk of disease recurrence and progression of intermediate and high-risk Non-Muscle Invasive Bladder Cancers (NMIBCs), intravesical adjuvant treatment with Bacillus Calmette-Guerin (BCG) represents the standard of care, although up to 50% of patients will eventually recur and up to 20% of them will progress to Muscle Invasive Bladder Cancer (MIBC). Radical Cystectomy (RC) is the treatment of choice in this setting; however, this represents a major and morbid surgery, thus meaning that not all NMIBCs patient could undergo or may refuse this procedure or may refuse. The search for effective bladder sparing strategies in NMIBCs BCG-unresponsive patients is a hot topic in the urologic field. AREAS COVERED: We aimed to review the most important bladder-preserving strategies for BCG unresponsive disease, from those used in the past, even though rarely used nowadays (intravesical chemotherapy with single agents), to current available therapies (e.g. intravesical instillation with Gemcitabine-Docetaxel), and to future upcoming treatments (Oportuzumab Monatox). EXPERT OPINION: At present, bladder-preserving treatments in BCG-unresponsive patients are represented by the use of intravesical instillations, systemic immunotherapies, both with good short-term and modest mid-term efficacy, and numerous clinical trials ongoing, with encouraging initial results, in which patients could be recruited.	bladder
Molecular findings and virological assessment of bladder papillomavirus infection in cattle.	Bovine and ovine papillomaviruses (BPVs - OaPVs) are infectious agents that have an important role in bladder carcinogenesis of cattle. In an attempt to better understand territorial prevalence of papillomavirus genotypes and gain insights into their molecular pathway(s), a virological assessment of papillomavirus infection was performed on 52 bladder tumors in cattle using droplet digital polymerase chain reaction (ddPCR), an improved version of conventional PCR. ddPCR detected and quantified BPV DNA and mRNAs in all tumor samples, showing that these viruses play a determinant role in bovine bladder carcinogenesis. OaPV DNA and mRNA were detected and quantified in 45 bladder tumors. BPV14, BPV13, BPV2, OaPV2, OaPV1, and OaPV3 were the genotypes most closely related to bladder tumors. ddPCR quantified BPV1 and OaPV4 DNA and their transcripts less frequently. Western blot analysis revealed a significant overexpression of the phosphorylated platelet derived growth factor β receptor (PDGFβR) as well as the transcription factor E(2)F(3), which modulate cell cycle progression in urothelial neoplasia. Furthermore, significant overexpression of calpain1, a Cys protease, was observed in bladder tumors related to BPVs alone and in BPV and OaPV coinfection. Calpain1 has been shown to play a role in producing free transcription factors of the E(2)F family, and molecular findings suggest that calpain family members work cooperatively to mutually regulate their protease activities in cattle bladder tumors. Altogether, these results showed territorial prevalence of BPV and OaPV genotypes and suggested that PDGFβR and the calpain system appeared to be molecular partners of both BPVs and OaPVs.	bladder
Amino-truncated NOV expression and its correlation with clinicopathologic features, prognosis, metastasis, and chemoresistance in bladder cancer.	Nephroblastoma, an overexpressed gene (NOV) protein, plays an important role in proliferation, differentiation, angiogenesis, adhesion, invasion and tumorigenesis, but the function of amino-truncated NOV is different. This study is to investigate the role of amino-truncated NOV in the progression of bladder cancer. Using immunohistochemistry and Western blot analysis, we detected the amino-truncated NOV in bladder cancer, and statistical analysis was performed to estimate the association between the expression of amino-truncated NOV and the patient's prognosis by SPSS 19.0. With transduction of amino-truncated NOV, we evaluated alteration for proliferation, migration, invasion and chemoresistance in bladder cancer cells, as well as some proteins related to Wnt/β-catenin pathway and epithelial-mesenchymal transition. The truncated variant of the NOV protein was located in a nucleus other than the cytoplasm and highly expressed in bladder cancer, which was also linked to higher pathological grade and positive lymph node metastasis as well as recurrence. The exact sequence of this truncated protein was confirmed, and it was a 26-kDa splicing. The truncated NOV protein found in bladder cancer was cut at the 187th amino acid of the full-length protein. It was also involved in bladder cancer progression and chemoresistance through a mechanism involving epithelial-mesenchymal transition (EMT) and the Wnt/β-catenin signaling pathway. Our findings provide experimental evidence that the nuclear NOV protein expression is a potential biomarker in the prognostic evaluation of bladder cancer and enhanced amino-truncated NOV expression is potentially important for bladder cancer cell invasion, metastasis and chemoresistance during progression.	bladder